NDUFA2

Chr 5

NADH:ubiquinone oxidoreductase subunit A2

Also known as: B8, CIB8, MC1DN13

The encoded protein is a subunit of NADH:ubiquinone oxidoreductase (complex I) in the mitochondrial electron transport chain and regulates complex I activity and assembly through redox processes. Biallelic mutations cause mitochondrial complex I deficiency, nuclear type 13, which presents as Leigh syndrome, an early-onset progressive neurodegenerative disorder. This condition follows autosomal recessive inheritance.

GeneReviewsResearchSummary from RefSeq, OMIM, UniProt
LOEUF 0.61
Clinical SummaryNDUFA2
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.
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ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 45 VUS of 121 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — NDUFA2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.61LOEUF
pLI 0.774
Z-score 2.05
OE 0.00 (0.000.61)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
-0.24Z-score
OE missense 1.09 (0.891.35)
62 obs / 56.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.000.61)
00.351.4
Missense OE1.09 (0.891.35)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 0 / 4.9Missense obs/exp: 62 / 56.9Syn Z: -0.72

ClinVar Variant Classifications

121 submitted variants in ClinVar

Classification Summary

Pathogenic15
VUS45
Likely Benign37
Benign14
Conflicting7
15
Pathogenic
45
VUS
37
Likely Benign
14
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
13
0
15
Likely Pathogenic
0
0
0
0
0
VUS
2
30
12
1
45
Likely Benign
0
0
25
12
37
Benign
0
0
12
2
14
Conflicting
7
Total2326215118

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NDUFA2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC